Respiratory Syncytial Virus (RSV) is a major cause of pneumonia in young children. Our experiments indicate that this organism interacts with monocytes to produce inflammatory cytokines which are important in the host response to infection. Monocytes are key components of the innate immune system in humans. These cells express an array of pattern recognition receptors and co-factors on their surface, including CD14 and Toll-like receptors (TLRs). The role of monocyte cell surface CD14 in the innate immune response to bacteria has been well documented. Recent studies suggest that TLR2 and TLR4 are important co-receptors for monocyte responses to lipopolysaccharide, lipopeptides and other microbial antigens. Our data indicate that TLR2, TLR4 and CD14 are important in the response to RSV. Using chimeric proteins and knock-out mice we will define the pathophysiology of the innate immune response to RSV and other viral pathogens, including Newcastle disease virus and polyoma virus. These studies should enable us to better understand the pathophysiology of viral infections.